ImmunoTargets and Therapy最新文献

The use of vaccines have resulted in a remarkable improvement in global health. It has saved several lives, reduced treatment costs and raised the quality of animal and human lives. Current traditional vaccines came empirically with either vague or completely no knowledge of how they modulate our immune system. Even at the face of potential vaccine design advance, immune-related concerns (as seen with specific vulnerable populations, cases of emerging/re-emerging infectious disease, pathogens with complex lifecycle and antigenic variability, need for personalized vaccinations, and concerns for vaccines' immunological safety -specifically vaccine likelihood to trigger non-antigen-specific responses that may cause autoimmunity and vaccine allergy) are being raised. And these concerns have driven immunologists toward research for a better approach to vaccine design that will consider these challenges. Currently, immunoinformatics has paved the way for a better understanding of some infectious disease pathogenesis, diagnosis, immune system response and computational vaccinology. The importance of this immunoinformatics in the study of infectious diseases is diverse in terms of computational approaches used, but is united by common qualities related to host-pathogen relationship. Bioinformatics methods are also used to assign functions to uncharacterized genes which can be targeted as a candidate in vaccine design and can be a better approach toward the inclusion of women that are pregnant into vaccine trials and programs. The essence of this review is to give insight into the need to focus on novel computational, experimental and computation-driven experimental approaches for studying of host-pathogen interactions and thus making a case for its use in vaccine development.

Physicians treating patients affected by nonmuscle-invasive bladder cancer (NMIBC) have been in shock during the last six years since manufacturing restrictions on the production of the first-option medicine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), have resulted in worldwide shortages. This shortage of BCG has led to a rethinking of the established treatment guidelines for the rationing of the administration of BCG. Some possible schedule modifications consist of a decrease in the length of maintenance treatment, a reduction in the dose of BCG in intravesical instillations or the use of different BCG substrains. All these strategies have been considered valuable in times of BCG shortage. In addition, the lack of availability of BCG has also led to the general recognition of the need to find new treatment options for these patients so that they are not dependent on a single treatment. Few alternatives are committed to definitively replacing BCG intravesical instillations, but several options are being evaluated to improve its efficacy or to combine it with other chemotherapeutic or immunotherapeutic options that can also improve its effect. In this article, we review the current state of the treatment with BCG in terms of all of the aforementioned aspects.

Varicella zoster virus (VZV) is the etiological agent of varicella, a highly infectious, self-limiting disease with serious complications. The decline in cell-mediated immunity (CMI) that occurs with aging or immunodepression causes a reactivation of the latent VZV as herpes zoster (HZ). Prevention of VZV through varicella vaccination strategies allows to avoid the primary infection in newborns and susceptible subjects. Available monovalent and combined VZV vaccines are effective, safe and generally well tolerated. Universal varicella vaccination has significantly impacted on incidence, complications and deaths related to this disease. Prevention of HZ through vaccination is a priority to avoid the significant burden of its incidence and complications. Currently two HZ vaccines are available. The recombinant zoster vaccine (RZV), approved by the FDA in 2017 and Zoster Vaccine Live (ZVL) licensed in the United States by the FDA in 2006. The advisory committee on immunization practices (ACIP) preferentially recommends RZV. ZVL remains an option for prevention of HZ in immunocompetent adults aged ≥60 years, although the CMI tends to wane a few years after vaccination.

Richter syndrome (RS) is recognized as the development of a secondary and aggressive lymphoma during the clinical course of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Most of such histological transformations are from RS to diffuse large B-cell lymphoma (DLBCL-RS, 90%) and Hodgkin's lymphoma (HL-RS, 10%). Histopathological examination is a prerequisite for diagnosis. It is crucial to assess the relationship between the RS clone and the underlying CLL/SLL because clonally related DLBCL-RS has a poor outcome, while clonally unrelated cases have a prognosis similar to de novo DLBCL. An anti-CD20 antibody-based immunochemotherapy is hitherto the frontline treatment of choice for DLBCL-RS; nonetheless, the results are unsatisfactory. Allogeneic stem cell transplantation should be offered to younger and fit patients as a consolidative treatment; however, the majority of the patients may not be qualified for this procedure. The HL-RS transformation has better outcomes than those of DLBCL-RS and can effectively be treated by the adriamycin, bleomycin, vinblastine, and dacarbazine regimen. Although novel agents are currently being investigated for RS, immunochemotherapy nevertheless remains a standard treatment for DLBCL-RS.

Background: T cell immunodeficiency is a common feature in patients with different kinds of hematological disease such as T cell non-Hodgkin lymphoma (T-NHL), B cells NHL (B-NHL), NK/T cell NHL (NK/T-CL) and acute myeloid leukemia (AML). In our recent research, we found that significantly lower expression levels in MALT1 and NF-κB were related to suppression of T cell activation. Therefore, this study was conducted to further investigate the role of downregulating MALT1 in the development of immunodeficiency in T cells.

Methods: We induced activation inhibition in CD3⁺ T cells by MALT1 knockdown. Then we characterized the gene expression profile after MALT1 suppression by microarray analysis.

Result: The differentially expressed genes were ZAP-70, p65, MDM2, ATM, NFATC2 which participate in the NF-κB, p53, and NFAT pathways in CD3⁺ T cells after MALT1 downregulation.

Conclusion: MALT1 suppression may contribute to immunodeficiency in T cells via suppression of T cell activation and proliferation pathways. These data may help to explain some of the characteristics of immunodeficiency of T cells.

Checkpoint immunotherapy uses highly selective humanized monoclonal antibodies against checkpoint signals such as programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1). By blocking these receptors and signals, the immune system can be reactivated to fight the tumor. Immunotherapy for advanced non-small cell lung cancer (NSCLC) has resulted in a new paradigm of treatment options resulting in improved survival and response rates and has a less severe yet unique toxicity profile when compared to chemotherapy. PD-1 inhibitors, nivolumab and pembrolizumab, and PD-L1 inhibitor, atezolizumab, are currently approved by regulatory authorities for the treatment of advanced NSCLC. This article provides a detailed review of these newer agents, their mechanism of action, side-effect profile, therapeutic indications and current evidence supporting their use in the management of NSCLC.